Genetic ablation of the isoform γ of PI3K decreases antidepressant efficacy of ketamine in male mice.

ABSTRACT: About one-third of major depressive disorder (MDD) patients demonstrate unresponsiveness to classic antidepressants, and even the clinical efficacy of fast-acting drugs such as ketamine varies significantly among patients with treatment-resistant depression. Nevertheless, the lack of suitable animal models that mimic a possible ketamine-resistant phenotype challenges the understanding of resistance to drug treatment. In this study, we showed that PI3Kγ knock-out (KO) mice do not respond to classical doses of ketamine and classical antidepressants. PI3Kγ KO mice were unresponsive to both the rapid and sustained antidepressant-like effects of a single dose of ketamine in the forced swimming test. Additionally, they were unresponsive to the antidepressant-like effects induced by the tricyclic

SUBMITTER: Vaz GN 

PROVIDER: S-EPMC11255840 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature